The in vitro serological detection of H-Y (male) antigen on the surface of mouse spermatozoa and male epidermal cells, with the cytotoxic test, provides the means for a closer evaluation of humoral versus cellular immune factors involved in H-Y incompatibility, and of other questions about the H-Y antigenic system. Our aims are to: (1) Use in vitro and in vivo assays to study the regulation of the cellular and humoral immune responses against the H-Y antigen as it relates to (a) the long-term survival of male grafts on certain strains of mice which nevertheless produce cytotoxic H-Y antibody, and (b) the specific tolerance of the H-Y antigen exhibited by multiparous females; 2) Determine to what extent there is polymorphism for H-Y within the species (mouse); 3) Determine whether or not antigenic representation on the sperm surface is coded by its haploid genotype; and 4) Develop procedures for the immunoselection of female embryos prior to implantation. In a broader context, in as much as H-Y incompatibility is now seen to be a system in which graft rejection may not occur despite an immune response (antibody production), it provides a parallel with the growth of antigenic tumors in hosts that produce antibody and therefore has relevance to cancer as well as to transplantation biology.